The development of materials that are capable of selectively detecting conformational changes in proteins, especially the formation of amyloid fibrils, have received increasing attention, owing to their large potential for being used as analytic tools in clinical chemistry. Amyloid fibrils are normally stained with small molecule dyes, such as Congo red and thioflavin T.
CPs based sensors are sensitive to very minor perturbations, due to amplification by a collective system response and therefore offer a key advantage compared to small-molecule based sensors. The possibility to use CPs as detecting elements for biological molecules requires that polymers are compatible with an aqueous environment. This has been accomplished by making conjugated (and sometimes luminescent) polyelectrolytes, as recently used to detect biomolecules through their impact on the conditions for photoinduced charge or excitation transfer.
CPs have previously been used to detect biospecific interactions, such as receptor/analyte interactions, through the conformational alterations of the polyelectrolyte chains [Nilsson, K. P. R.; Inganäs, O. Nature Materials 2003, 2, 419-424; Ho, H-A. et. al. Angew. Chem. Int. Ed. 2002, 41, 1548; Ho, H-A.; Leclerc, M. J. Am. Chem. Soc. 2004, 126, 1384; Dore, K.; Dubus, S.; Ho, H-A.; Levesque, I.; Brunette, M.; Corbeil, G.; Boissinot, M.; Boivin, G.; Bergeron, M. G.; Boudreau, D.; Leclerc, M. J. Am. Chem. Soc. 2004, 126, 4240; WO02/081735, WO03/096016].
However, the use of CPs as direct probes for the recording of conformational changes and self-assembly/aggregation of proteins, especially the formation of amyloid fibrils, has never been reported.
A need exists for simpler and more sensitive methods for detection of conformational changes and self-assembly/aggregation of proteins, especially the formation of amyloid fibrils. Methods based on CPs that can interact directly with proteins and transduce the conformational alteration of the protein into optical signals, would therefore be desirable.